Cockayne syndrome group B protein stimulates repair of formamidopyrimidines by NEIL1 DNA glycosylase
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Cockayne syndrome group B protein stimulates repair of formamidopyrimidines by NEIL1 DNA glycosylase. / Muftuoglu, Meltem; de Souza-Pinto, Nadja C; Dogan, Arin; Aamann, Maria; Stevnsner, Tinna; Rybanska, Ivana; Kirkali, Güldal; Dizdaroglu, Miral; Bohr, Vilhelm A.
In: Journal of Biological Chemistry, Vol. 284, No. 14, 04.2009, p. 9270-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cockayne syndrome group B protein stimulates repair of formamidopyrimidines by NEIL1 DNA glycosylase
AU - Muftuoglu, Meltem
AU - de Souza-Pinto, Nadja C
AU - Dogan, Arin
AU - Aamann, Maria
AU - Stevnsner, Tinna
AU - Rybanska, Ivana
AU - Kirkali, Güldal
AU - Dizdaroglu, Miral
AU - Bohr, Vilhelm A
PY - 2009/4
Y1 - 2009/4
N2 - Cockayne syndrome (CS) is a premature aging condition characterized by sensitivity to UV radiation. However, this phenotype does not explain the progressive neurodegeneration in CS patients. It could be due to the hypersensitivity of CSB-deficient cells to oxidative stress. So far most studies on the role of CSB in repair of oxidatively induced DNA lesions have focused on 7,8-dihydro-8-oxoguanine. This study examines the role of CSB in the repair of formamidopyrimidines 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 4,6-diamino-5-formamidopyrimidine (FapyAde), which are substrates for endonuclease VIII-like (NEIL1) DNA glycosylase. Results presented here show that csb(-/-) mice have a higher level of endogenous FapyAde and FapyGua in DNA from brain and kidney than wild type mice as well as higher levels of endogenous FapyAde in genomic DNA and mtDNA from liver. In addition, CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells. When CSB and NEIL1 are depleted from HeLa cells by short hairpin RNA knockdown, repair of induced FapyGua is strongly inhibited. These results suggest that CSB plays a role in repair of formamidopyrimidines, possibly by interacting with and stimulating NEIL1, and that accumulation of such modifications may have a causal role in the pathogenesis of CS.
AB - Cockayne syndrome (CS) is a premature aging condition characterized by sensitivity to UV radiation. However, this phenotype does not explain the progressive neurodegeneration in CS patients. It could be due to the hypersensitivity of CSB-deficient cells to oxidative stress. So far most studies on the role of CSB in repair of oxidatively induced DNA lesions have focused on 7,8-dihydro-8-oxoguanine. This study examines the role of CSB in the repair of formamidopyrimidines 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 4,6-diamino-5-formamidopyrimidine (FapyAde), which are substrates for endonuclease VIII-like (NEIL1) DNA glycosylase. Results presented here show that csb(-/-) mice have a higher level of endogenous FapyAde and FapyGua in DNA from brain and kidney than wild type mice as well as higher levels of endogenous FapyAde in genomic DNA and mtDNA from liver. In addition, CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells. When CSB and NEIL1 are depleted from HeLa cells by short hairpin RNA knockdown, repair of induced FapyGua is strongly inhibited. These results suggest that CSB plays a role in repair of formamidopyrimidines, possibly by interacting with and stimulating NEIL1, and that accumulation of such modifications may have a causal role in the pathogenesis of CS.
KW - Adenosine Triphosphatases
KW - Animals
KW - DNA
KW - DNA Glycosylases
KW - DNA Helicases
KW - DNA Repair
KW - DNA Repair Enzymes
KW - DNA-(Apurinic or Apyrimidinic Site) Lyase
KW - Hela Cells
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Protein Binding
KW - Pyrimidines
KW - Substrate Specificity
U2 - 10.1074/jbc.M807006200
DO - 10.1074/jbc.M807006200
M3 - Journal article
C2 - 19179336
VL - 284
SP - 9270
EP - 9279
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 14
ER -
ID: 32446859